Assessing the Effects of Increased Mitochondrial Function Exercise Training on Muscle Performance (Rejuvenate2)

Assessing the Effects of Increased Mitochondrial Function and Chronic Aerobic or Resistance Exercise Training on Skeletal Muscle Performance in Older Men; a Pilot Study

As people grow older skeletal muscle gradually becomes smaller and weaker, causing reduced mobility and quality of life. To understand and reverse this negative process investigators need to find new ways of improving the ability of muscle to perform physical activity. There is some evidence that supplements may improve how the mitochondria work, and investigators want to explore this idea in more detail. This is possible by measuring how the muscles work and respond to exercise before and after taking the supplement alongside an aerobic (i.e. cycling) and resistance (i.e. weight lifting) exercise programme. This will give us the basic information investigators would need to see if this is a useful idea.

Study Overview

• Status: Terminated
• Conditions: Impaired Mitochondrial Function, Muscle Performance
• Intervention / Treatment: Dietary supplement: Acipimox; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • NIHR Exeter Clinical Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 75 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male
• Age between 65-75 years
• Body mass index between 19-29
• No active cardiovascular or metabolic disease
• No active respiratory disease
• No current musculoskeletal injuries
• A sedentary lifestyle (i.e. does not engage in strenuous, planned physical activity)
• The ability to give informed consent

Exclusion Criteria:

• Currently taking a statin drug or NSAIDs
• Have a current peptic ulcer
• Have any renal impairment
• Have a known hypersensitivity to Acipimox
• Suffer from vertigo
• Smoker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acipimox plus exercise training; The active supplement will contain the prescription drug Acipimox (250 mgs) , a nicotinic acid precursor traditionally used to lower blood lipid levels. The supplement will be administered 3 times per day, for 6 weeks.	Dietary supplement: Acipimox; Acipimox plus exercise training: Oral supplement containing Acipimox 250mgs as the active ingredient in blinded label tablet form.
Placebo Comparator: Placebo plus exercise training; The placebo supplement will contain only cellulose microcrystalline. This is an inert substance widely used in many pill and tablet formulations. It is an insoluble fibre and is not absorbed into the blood stream therefore is unlikely to cause toxicity when taken orally.	Dietary supplement: Placebo; Alternate unilateral resistance and aerobic exercise training will also be performed 5 times per week for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mitochondrial function	Mitochondria will be extracted from muscle samples immediately post-biopsy (biopsies taken baseline, week 3 and week 6) and analysed for content and subsequently for oxidative respiratory function using the Oroboros technique, and maximal rates of Adenosine Triphosphate (ATP) production.	Baseline, 3 weeks, 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic changes in habitual muscle protein synthetic rates	Baseline saliva samples then frequent saliva samples over 6 weeks following oral ingestion of the stable isotope deuterium oxide (D2O, or 'heavy water') will be analysed by gas-chromatography-pyrolysis-isotope ratio mass-spectrometry. analysis. Muscle samples collected at baseline, 3 weeks, 6 weeks will also be analysed by gas-chromatography-pyrolysis-isotope ratio mass-spectrometry	Baseline, 3 weeks and 6 weeks

Collaborators and Investigators

• Sponsor: University of Exeter
• Collaborators: Royal Devon and Exeter NHS Foundation Trust
• Investigators: Principal Investigator: Colleen Deane, PhD, University of Exeter

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2018
• Primary Completion (Actual): September 16, 2019
• Study Completion (Actual): September 16, 2019

Study Registration Dates

• First Submitted: October 25, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 30, 2017

Study Record Updates

• Last Update Posted (Actual): September 27, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Acipimox
• Other Study ID Numbers: 1617/024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No